There is intense interest in the pharmaceutical field in the development of synthetic routes for the conversion of penicillins to cephalosporin antibiotics.
3-Methylene cephalosporins of the formula ##STR2## are known to be useful intermediates for the preparation of cephalosporin antibiotics that are effective against gram-negative bacteria such as Escherichia coli, Broteus vulgaris, Proteus mirabilis, Proteus morganii, Salmonella schonmuelleri, Klebsiella pneumoniae AD, Klebsiella pneumoniae B, and Paracolobactrum arizoniae and gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae; see, for example, U.S. Pat. No. 3,883,518 issued May 13, 1975 to Ponticello et al. In formula I, and throughout the specification, the symbol R.sub.1 can be an acyl group, R.sub.2 can be hydrogen or .alpha.-methoxy, and R.sub.3 can be hydrogen, alkyl of 1 to 4 carbon atoms, 2,2,2-trichloroethyl, trimethylsilyl, diphenylmethyl, benzyl, 4-methoxybenzyl, or 4-nitrobenzyl.
The treatment of a 3-methylene cephalosporin of formula I with an organic base promotes isomerization to useful desacetoxy cephalosporins; see, for example, Chauvette et al., J. Org. Chem., 38, 2994 (1973). The oxidative fission of 3-methylene cephalosporins of formula I provides useful 3-hydroxy cephems; see, for example, Netherlands patent 7309136.